ChIP-chip from human fetal brain with H3K27Ac and H3K4Me1. Homo sapiens

Enhancers can regulate the transcription of genes over long genomic distances. This is thought to lead to selection against genomic rearrangements within such regions that may disrupt this functional linkage. We tested this concept experimentally using the human X chromosome. We describe a scoring method to identify evolutionary maintenance of linkage between conserved non-coding elements and neighbouring genes. Chromatin marks associated with enhancer function are strongly correlated with the linkage score. We tested more than 1,000 putative enhancers by transgenesis assays in zebrafish to ascertain the identity of the target gene, with a focus on genes involved in X-linked intellectual disabilities (ID). The majority of active enhancers drive a transgenic expression in a pattern consistent with the known expression of a linked gene. These results show that evolutionary maintenance of linkage is a reliable predictor of an enhancer's function, and provide new information to discover the genetic basis of diseases caused by the mis-regulation of gene expression. Overall design: ChIP-chip from human fetal brain using H3K27Ac or H3K4Me1 antibodies. Biological replicates: H3K27Ac_Rep1, H3K27Ac_Rep2 Biological replicates: H3K4Me1_Rep1, H3K4Me1_Rep2